This invention is in the field of medical procedures, namely, procedures facilitated primarily by laser medical equipment used in the delivery of pharmaceuticals or the removal of biomolecules, fluids or gases.
The traditional method for the collection of small quantities of fluids or gases from a patient utilizes mechanical perforation of the skin with a sharp device such as a metal lancet or needle. Additionally, the typical method of administering local anesthetic is through the use of a needle. These procedures have many drawbacks, two of which are the possible infection of health-care workers or the public at large with the device used to perforate the skin, and the costly handling and disposal of biologically hazardous waste.
When skin is perforated with a sharp device such as a metal lancet or needle, biological waste is created in the form of the xe2x80x9csharpxe2x80x9d which is contaminated by the patient""s blood and/or tissue. If the patient is infected with any number of blood-born agents, such as human immunodeficiency virus (HIV) which causes acquired immune deficiency syndrome (AIDS), hepatitis virus or the etiological agent of other diseases, the contaminated sharp can pose a serious threat to others who come in contact with it. There are many documented instances of HIV infection of medical workers who were accidentally stabbed by a contaminated sharp.
Disposal of sharps is also a major problem. Disposal of contaminated materials poses both a logistic and a financial burden on the end user such as the medical institution. In the 1980s, numerous instances of improperly disposed biological wastes being washed up on public beaches occurred. The potential for others, such as intravenous drug users, to obtain improperly disposed needles is also problematic.
There exists additional drawbacks to the traditional method of stabbing a patient with a sharp instrument for the purpose of delivering pharmaceutical agents or for drawing fluids or gases. Often, the stabbing procedure must be repeated, often resulting in significant stress and anxiety in the patient. The pain associated with being stabbed by a sharp instrument can be a traumatizing procedure, especially in pediatric patients. This can cause significant stress and anxiety in the patient.
Clearly the current procedure for puncturing skin for the purpose of drawing fluids or gases has significant inherent problems. These problems arise because a sharp instrument is used in the procedure. Thus, a need exists for techniques to remove biomolecules, fluids or gases, and to administer pharmaceutical agents, which do not use a sharp instrument. Such methods would obviate the need for disposal of contaminated instruments, and reduce the risk of cross infection.
The current technology for applying pharmaceutical substances without the use of needles typically involves: (a) drug mixtures in creams, lotions or gels; (b) iontophoresis; (c) carriers or vehicles which are compounds that alter the chemical properties of either the stratum corneum or the pharmaceutical; (d) sonophoresis which involves altering the barrier function of stratum corneum by ultrasound; or (e) drug patches which attach to the skin to effect transdermal administration. For example, lidocaine is commonly used as a local anesthetic, especially in pediatric patients, but requires a cream to be applied for up to 60 minutes, and anesthesia is produced to a depth of only about 4 mm. The lack of penetration is a consequence of the barrier function of the stratum corneum. Inherent problems with iontophoresis include the complexity of the delivery system, cost, and unknown toxicology of prolonged exposure to electrical current. Additionally, the use of carriers or vehicles involves the use of an additional compound which right alter the pharnacokinetics of the pharmaceutical of interest. Finally, most patch applications are insufficient because many drugs do not easily traverse the stratum corneum.
Clearly a need exists for a means to apply pharmaceutical substances without the use of a needle. The current procedure for applying pharmaceuticals without the use of a needle puncture has inherent problems. The discoveries disclosed herein reduce or eliminate the problems associated with disposal of contaminated needles or sharps, reduce or eliminate the pain associated with being stabbed by a sharp instrument, and improve transdermal delivery of drugs.
Lasers have been used in recent years as a very efficient and precise tool in a variety of surgical procedures. Among potentially new sources of laser radiation, the rare-earth elements are of major interest for medicine. The most promising of these is a YAG (yttrium, aluminum, garnet) crystal doped with erbium (Er) ions. With the use of this crystal, it is possible to build an Erbium: YAG (Er:YAG) laser which can be configured to emit electromagnetic energy at a wavelength (2.94 microns) which is strongly absorbed by water. When tissue, which consists mostly of water, is irradiated with radiation at or near this wavelength, it is rapidly heated. If the intensity of the radiation is sufficient, the heating is rapid enough to cause the vaporization of tissue. Some medical uses of Er:YAG lasers have been described in the health-care disciplines of dentistry, gynecology and ophthalmology. See, e.g., Bogdasarov, B. V., et al., xe2x80x9cThe Effect of YAG:Er Laser Radiation on Solid and Soft Tissues,xe2x80x9d Preprint 266, Institute of General Physics, Moscow, 1987; Bol""shakov, E. N. et al., xe2x80x9cExperimental Grounds for YAG:Er Laser Application to Dentistry,xe2x80x9d SPIE 1353:160-169, Lasers and Medicine (1989).
Er:YAG lasers, along, with other solid state lasers often employ a polished barrel crystal element such as a polished rod. A laser built with such a polished element maximizes the laser""s energy output. Other lasers employ an entirely frosted element, normally with matte of about 50-55 microinch. However, in both cases, the energy output is typically separated into a central output beam surrounded by halo rays, or has an otherwise undesirable mode. Since it is extremely difficult to focus halo rays to a specific spot, the laser output may be unacceptable for specific applications.
Solid state lasers also typically employ two optic elements in connection with the crystal element. The optic elements consist of the rear (high reflectance) mirror and the front partial reflectance mirror, also know as an output coupler. The crystal element and the optic elements are rigidly mounted in order to preserve the alignment between them. However, changes in temperature, such as that caused by expansion of the crystal rod during flash lamp exposure, also cause shifts in alignment between the mirrors and the crystal. The misalignment of the mirrors and the crystal element results in laser output energy loss. Thus, the rigidly mounted elements require constant adjustment and maintenance. Moreover, thermal expansion of the crystal element during lasing can cause the crystal to break while it is rigidly -attached to a surface with different expansion characteristics.
The present invention primarily employs a laser to perforate, ablate or alter one or more layers of the skin of a patient in order to remove biomolecules, fluids or gases, or to administer pharmaceutical substances. Alteration of a patient""s skin is produced by irradiating the surface of the skin by a pulse of electromagnetic energy emitted by a laser. Such irradiation may merely enhance the permeability of the stratum corneum without causing ablation (vaporization) or perforation of tissue; alternatively, it may enhance the skin""s permeability by ablating or perforating the stratum corneum, or it may enhance the permeation of molecules by altering such intercellular or intracellular molecules. It is possible to very precisely alter skin or permeability to a selectable extent without causing clinically relevant damage to healthy proximal tissue; the depth and extent of alteration may be accomplished by a judicious selection of the following irradiation parameters: wavelength, energy fluence (determined by dividing the energy of the pulse by the area irradiated), pulse temporal width and irradiation spot size.
A pulsed laser beam may be focused to a small spot for the purpose of perforating or altering tissue. By adjusting the output of the laser, the depth, width and length of the perforation or alteration can be controlled to fit the purpose for which the perforation or alteration is required. Alternatively continuous-wave or diode lasers may be used to duplicate the effect of a pulsed laser beam. These modulated lasers are controlled by Q-switching or gating the output of a continuous wave laser or fluctuating the output excitation current in a diode laser. In either case the overall effect is to achieve brief irradiation, or a series of brief irradiations, that produce the same controlled tissue permeabilizing effect as a pulsed laser.
This invention provides a means for perforating or altering the skin of a patient in a manner that does not result in bleeding. The perforation or alteration created typically penetrates through the stratum corneum layer, or both the stratum corneum layer and the epidermis, reducing or eliminating the barrier function of the stratum corneum. This will allow the administration of substances such as pharmaceuticals through the skin, or the removal of biomolecules, fluids or gases. There are several advantages to administering drugs in this fashion, for example: drugs can be administered continually on an out-patient basis over long periods of time, and the speed and/or efficiency of drug delivery can be enhanced for drugs which are either slow or unable to penetrate skin. Furthermore, this method of delivery provides an alternative delivery route for drugs that would otherwise require to be injected, eliminating the pain associated with needle punctures. Furthermore, the reduced barrier properties of the stratum corneum allow the taking of measurements of various fluid constituents, such as glucose, or to conduct measurements of gases.
Perforation involves the complete ablation of all layers of the stratum corneum to reduce or eliminate its barrier function. Ablation may also be characterized as partial when less than all layers of the stratum corneum are ablated, leaving sufficient tissue intact to substantially maintain the barrier function. For the purpose of this application, xe2x80x9cperforationxe2x80x9d will mean only the complete ablation of all layers of the stratum corneum; xe2x80x9cablationxe2x80x9d may mean, depending upon the context, either partial ablation or perforative ablation. Certain laser-induced alterations of molecules in the stratum corneum or interstitial spaces may also occur without actual ablation, and this will result in enhanced permeation of substances into or out of the body through the skin. A pulse or pulses of infrared laser irradiation at a subablative energy of, for example, 60 mJ per 2 mm spot, reduces or eliminates the barrier function of the stratum corneum and increases permeability without actually ablating or perforating the stratum corneum itself. The technique may be used for transdermal delivery of drugs or other substances, or for obtaining samples of biomolecules, fluids or gases from the body. Different wavelengths of laser radiation and energy levels less than or greater than 60 mJ may also produce the enhanced permeability effects without ablating the skin.
For the purpose of this application, the terms xe2x80x9cirradiationxe2x80x9d or xe2x80x9calteration,xe2x80x9d or a derivative thereof, will generally mean perforation, ablation or modification which results in enhanced transdermal permeation of substances. The term xe2x80x9cenergized sitexe2x80x9d means the volume of tissue exposed to energy intended to enhance transdermal permeation of substances.
The mechanism for non-ablative alteration of the stratum corneum is not certain. It may involve changes in lipid or protein nature or function or from desiccation of the skin. Regardless, laser-induced alteration changes the permeability parameters of the skin in a manner which allows for increased passage of fluids and gases across the stratum corneum. This invention avoids the use of sharps such as needles, normally needed for drug administration or sample extraction. The absence of a contaminated sharp will eliminate the risk of accidental injury and its attendant risks to the health care worker, the patient, and anyone who may come into contact with the sharp, whether by accident or by necessity.
The absence of sharps also obviates the need for disposal of biologically hazardous waste. Thus, this invention provides an ecologically sound method of perforating or altering skin.
A typical laser can further be modified to include a container unit. Such a container unit can be added to: (1) increase the efficiency in the collection of fluids or gases; (2) reduce the noise created when the laser beam perforates the patient""s tissue; and (3) collect the ablated tissue. The optional container unit is optionally evacuated to expedite the collection of the released materials such as the fluids or gases. The container can also be used to collect only ablated tissue. The noise created from the laser beam""s interaction with the patient""s skin may cause the patient anxiety. The optional container unit reduces the noise intensity and therefore alleviates the patient""s anxiety and stress. The container unit also minimizes the risk of cross contamination and guarantees the sterility of the collected sample. The container also serves to attenuate and/or absorb any stray, potentially-hazardous electromagnetic radiation. The placement of the container unit in the use of this invention is unique in that it covers the tissue being punctured, at the time of puncture by the laser beam, and is therefore able to collect the fluid or gas samples and/or ablated tissue as the perforation or alteration occurs.
A typical laser used for this invention requires no special skills to use. It can be small, light-weight and can be used with regular or rechargeable batteries. The greater the laser""s portability and ease of use, the greater the utility of this invention in a variety of settings, such as a hospital room, clinic or home.
Safety features can be incorporated into the laser that require that no special safety eyewear be worn by the operator of the laser, the patient, or anyone else in the vicinity of the laser when it is being used.